Novel mercaptoderivatives of ionones and irones

ABSTRACT

WHEREIN R1 REPRESENTS A HYDROGEN ATOM OR THE METHYL GROUP AND WHEREIN THE BRROKEROKEN LINES DENOTE A DOUBLE BOND WHICH IS PRESENT IN ONE OF THE THREE INDICATED POSITIONS. 1. A COMPOUND HAVING THE GENERAL FORMULA   1-R1,2,2-DI(H3C-),3-(H3C-CO-CH2-CH(-SH)-),4-(H3C- OR H2C=)   CYCLOHEX-3 OR 4-ENE

United States Patent Oflice Patented Oct. 29, 1974 US. Cl. 260-586 R 2 Claims ABSTRACT OF THE DISCLOSURE There are disclosed novel mercapto and acetyl mercapto derivatives of ionones and irones. These compounds possess interesting properties as odorants and flavorants. The nature of these odorant and fiavorant properties is drastically modified when they are compounded with ionones or irones.

FIELD OF THE INVENTION Novel sulfur containing ionone and irone derivatives.

SUMMARY OF THE INVENTION The ionone and irone derivatives provided by the present invention have the following general formula SRO HSR (III) wherein R has the significance given earlier, to the double bond situated in the side-chain of a compound of formula II hereinbelow O ll Rl A/\ wherein R and the broken lines are as defined hereinabove.

Or, for the manufacture of a derivative of formula I in which R represents a hydrogen atom, cleaving off the acetyl group from a corresponding derivative of formula I in which R represents the acetyl group.

The ionone and irone derivatives of formula I hereinbefore are distinguished by particular fragrance and/or flavor properties on the basis of which they can be used in odorant and/or flavoring compositions, especially those with berry and/ or floral notes.

On the basis of their interesting aroma properties, the certain derivatives can be used for generating raspberry aromas in foodstuffs (e.g. milk drinks, yoghurt etc.), in delicacies (e.g. confectionery products such as bonbons) and in beverages (e.g. table water, mineral water etc.). Their pronounced aromatic qualities enable them to be used in small concentrations (e.g. in the range of 0.1 p.p.m.1 wt. percent, preferably in the range of 10-500 p.p.m.).

DESCRIPTION OF THE PREFERRED EMBODIMENTS Derivatives of the general formula COCH:

. (Ib) wherein R and the broken lines have the significance given in connection with formula I hereinbefore,

can be manufactured by reacting a compound of formula II with thioacetic acid, expediently in the presence of a catalyst favoring the formation of radicals. Such catalysts are, for example, azodiisobutyronitrile, ascaridol or customary peroxides. However, the reaction can also be initiated by the action of rays of the ultraviolet or visible range. The reaction temperature expediently lies between about 0 C. and 150 C., preferably between about C. and C.

Derivatives of the general formula SHO wherein R and the broken lines have the significance given in connection with formula I hereinbefore,

can, as mentioned earlier, be manufactured either by (a) reacting a compound of formula II with hydrogen sulphide or by (b) cleaving off the acetyl group from a derivative of formula Ib, expediently under acidic or mild alkaline conditions.

The reaction of a compound of formula II with hydrogen sulphide is expediently effected in the presence of a base such as an alkali metal hydroxide (e.g. sodium hydroxide or potassium hydroxide), an alkaline earth metal hydroxide (e.g. calcium hydroxide) or an organic base such as an amine (e.g. a dialkylamine such as diethyl amine, a trialkylamine such as triethylamine or a heterocyclic amine such as piperidine). .As solvent there can be used, for example, ethanol. The reaction can be carried out at a temperature between about 0 C. and 100 C. Temperatures in the range of about 4060 C. are preferred. In other respects, the reaction can be carried out under normal pressure or expediently under elevated pressure, i.e. in a sealed vessel, since the reaction proceeds with diminution of volume.

The acid cleavage of the acetyl group from a deriva tive of formula Ib is expediently carried out in the pres ence of a Lewis acid such as boron trifluoride or boron trichloride. As the solvent there can be used, for example, methanol 01' ether. This cleavage can be carried out at a temperature between about -20 C. and 100 C., preferably between 10 C. and 50 C. The pressure is not critical, but for the sake of convenience it is preferred to carry out this cleavage under normal pressure. The acetyl group can also be cleaved off from a derivative of formula Ib under mild alkaline conditions. Suitable bases for this purpose are alkali metal hydroxides (e.g. sodium hydroxide or potassium hydroxide), alkaline earth metal hydroxides (e.g. calcium hydroxide), alkali metal carbonates (e.g. sodium carbonate), alkali metal bicarbonates (e.g. sodium bicarbonate) and the like. As the solvent there can be used lower alkanols such as methanol or ethanol, water or mixtures thereof. This alkaline cleavage can be carried out at a temperature between about C. and 100 C., preferably between 40 C. and 60 C. The pressure is not a critical factor, but it is, however, preferred to carry out this alkaline cleavage under normal pressure.

The aforementioned cleavage of the acetyl group from a derivative of formula Ib proceeds non-quantitatively under both the acidic and the alkaline conditions and yields, in addition to starting material and the desired product, the corresponding compound of formula II.

A particular embodiment of the present invention is concerned with ionone derivatives of the general formula wherein R has the significance given earlier and the broken lines denote a double bond which is present in one of the three indicated positions,

especially those ionone derivatives of formula Ia in com bination with a compound of the general formula (Ila) wherein the broken lines denote a double bond which is present in one of the two indicated positions.

It will be appreciated that in the combination of an ionone or irone derivative of formula I on the one hand with a compound of formula II on the other hand the significance of R and/ or the position of the double bond denoted by the broken lines need not be identical.

In accordance with the present invention it has been surprisingly found, for example, that mixtures of a-ionone (a) with 4 (1,1,3 trimethyl 3-cyclohexen-2-yl)-4- acetyl-mercapto-butanone-2 (b) and/or particularly with 4 (1,1,3 trimethyl 3-cyclohexen-2-yl)-4-mercaptobutanone-2 (e) have a pronounced raspberry aroma, that is to say, the aroma of freshly pressed raspberries. This finding is completely unexpected insofar as the ordor of w and ,B-ionone can hardly be denoted as raspberry-like and, above all, the fragrances of the two individual components (b) and (c) are in no way reminiscent of raspberries, as can be seen from the following fragrance characterization: Acetylmercapto derivative (b): Sulphurlike, reminiscent of leeks, slightly woody. Mercapto derivative (c): Green, sulphurous with a woody under-tone.

The odor of raspberries occurs with mixtures of the most varied composition. Practical mixtures a+b, a+c or a-l-b-l-c in percentages by weight (prefered values in brackets) are given in the following table:

For the olfactory evaluation of these mixtures there were used 10% solutions in ethanol (fragrance test) or aqueous sugar solutions containing 0.1 ml. of the fragrance test solution per ml. of sugar solution (flavor test).

However, the ionone and irone derivatives of formula I hereinbefore also possess advantageous properties in compositions of quite different character (e.g. in compositions with floral note) since they are capable of modifying the fragrance of such compositions in a desirable manner. They can accordingly also be used as odorants for the production of perfumes, especially those with woody and floral notes. For this purpose, they can be used in an amount in the range of about 0.001-5 Wt. percent, preferably about 0.01-1 wt. percent. In addition to actual perfumes, such odorant compositions can also be used as bases for the perfurning of products such as solid and liquid detergents, synthetic washing agents, aerosols and cosmetic articles of all kinds (e.g. soaps, lotions, creams etc.). In addition, the ionone and irone derivatives of formula I are also distinguished by superior adhesiveness.

The following examples illustrate the process provided by the present invention:

EXAMPLE 1 50 g. of u-ionone are dissolved in 50 ml. of thioacetic acid and treated with 250 mg. of azodiisobutyronitrile. The mixture is heated at C. under reflux for 18 hours, subsequently cooled in ice-water and taken up in 4 litres of ether. The ethereal solution is washed once in 250 ml. of saturated aqueous sodium chloride solution, then twice with 250 ml. of saturated aqueous sodium bicarbonate solution each time and a further three times with 250 ml. of saturated aqueous sodium chloride solution each time. The organic phase is dried over magnesium sulphate and the ether distilled off under a vacuum. There results a crude product (91 g.) which is fractionally distilled at 0.1 mm. Hg. The fractions free from ot-iOIlOI'lC are combined and crystallized from hexane at -70 C. There are obtained 33.5 g. of 4-(1,1,3-trimethy1- 3-cyclohexen-2-yl)-4-acetylmercapto-butanone-Z of melting point 57-58 C. and boiling point C./0.1 mm. Hg, in the form of two diastereomers in the ratio 1:1.

Fragrance of the product: sulphur-like, reminiscent of leeks, base slightly woody.

EXAMPLE 2 48 g. of a-ionone are treated with a solution of 4 g. of potassium hydroxide in 40 ml. of absolute ethanol and cooled to -75 C. At this temperature, 40 ml. of hydrogen sulphide are condensed in over the course of 1 hour. The reaction solution is rapidly transferred into a pre-cooled autoclave and allowed to stand at room temperature for 20 hours, the pressure rising to 20 atmospheres. During two hours, the autoclave is heated to 50 C. (internal temperature), whereby the pressure increases to 28 atmospheres. It is subsequently cooled to 10 C., the excess hydrogen sulphide evaporated off and the residual reaction mixture taken up in 3 litres of ether. The ethereal solution is washed four times with 250 ml. of saturated aqueous sodium chloride solution each time and then dried over anhydrous magnesium sulphate. After distillation of the ether under a vacuum, there remains a crude product (51.5 g.) which, according to gaschromatographic analysis, consists of 33% u-ionone and 67 4-( 1,1,3-trimethyl-3-cycl0hexen-2-yl) -4-mercapto butanone-2 (in the form of two disastereomers in the ratio 12:1). The crude product is fractionally distilled over 1 g. of BHT (2,S-di-t-butyl-p-cresol), whereby there are obtained 38 g. of 4-(1,1,3-trimethyl-3-cyclohexen-Z-yl)-4- mercapto-butanone-Z of boiling point 80 C./0.07 mm. Hg.

Fragrance of the product: Green, sulphurous with a woody under-tone in the direction of ionone. After 18 hours, vitamin B odour with ionone-like accent.

EXAMPLE 3 100 g. of fi-ionone are dissolved in 100 ml. of thioacetic acid and treated with 250 mg. of azodiisobutyronitrile. The mixture is heated at 115 C. under reflux for 20 hours, subsequently cooled in ice-water and taken up in 4 litres of ether. The ethereal solution is Washed once with 250 ml. of saturated aqueous sodium chloride solution, then twice with 250 ml. of saturated aqueous sodium bicarbonate solution each time and a further three times with 250 ml. of saturated aqueous sodium chloride solution each time. The organic phase is dried over magnesium sulphate and the ether distilled 01f under a vacuum. There results a crude product (131 g.) which is fractionally distilled at 0.1 mm. Hg. The fractions containing the desired product are combined and crystallized from hexane at 70 C. There are thus obtained 71.5 g. of 4-(1,1,3-trimethyl-2-cyclohexen 2 yl) 4 acetylmercaptobutanone-2 of melting point 3133 C. and boiling point 112 C./0.1 mm. Hg.

EXAMPLE 4 1 g. of 4-(1,1,3-trimethyl-3-cyclohexen-2-yl)-4-acetylmercapto-butanone-Z is dissolved in 10 ml. of saturated aqueous sodium bicarbonate solution. The solution is heated at 50 C. for 1 hour, subsequently cooled in icewater and taken up in 200 ml. of ether. The ethereal solution is washed three times with 50 ml. of saturated aqueous sodium chloride solution each time, dried over anhydrous magnesium sulphate and the ether is distilled oif under a vacuum. According to gas-chromatographic analysis the product (0.91 g.) has the following composition:

Percent 4 (1,1,3 trimethyl 3 cyclohexen 2 yl) 4- acetylmercapto-butanone-2 81 4 1,1,3 trimethyl 3 cyclohexen 2 yl) 4- mcrcapto-butanone-Z EXAMPLE 5 A solution of 1 g. of boron trifluoride in ml. of methanol is treated under a nitrogen atmosphere with 2 g. of 4-(1,1,3-trimethyl-3-cyclohexen-2-yl)-4-acetylmercapto-butanone-2 and the mixture is stirred at C. for 17.5 hours. Subsequently, 20 m1. of ether and 50 ml. of water are added and the emulsion obtained is taken up in 500 ml. of ether. The ethereal solution is washed five times with 50 m1. of water each time, dried over magnesium sulphate and concentrated in a vacuum at 45 C. There results a crude product (1.83 g.) which, according to gas-chromatographic analysis, contains 26% of 4-(1,1, 3-trimethyl-3-cyclohexen-2-yl) 4 mercapto-butanone-2. This can be separated from starting material which is will present according to usual methods.

EXAMPLE 6 20.6 g. of [3-irone are treated with a solution of 1.6 g. of potassium hydroxide in 16 ml. of absolute ethanol and cooled to 75 C. At this temperature, 40 ml. of hydrogen sulphide are condensed in over the course of 1 hour. The reaction solution is rapidly transferred into a pre-cooled autoclave and allowed to stand at room temperature for 1 hour.

During two hours, the autoclave is heated to 50 C. (internal temperature), whereby the pressure increases to 21 atmospheres. It is subsequently cooled to 10 C., the excess hydrogen sulphide evaporated oil and the residual reaction mixture taken up in 3 litres of ether. The ethereal solution is washed four times with 250 ml. of saturated aqueous sodium chloride solution each time and then dried over anhydrous magnesium sulphate. After distillation of the ether under a vacuum, there remains a crude product (19.9 g.) which, according to gas-chromatographic analysis, consists of 39% fl-irone and 61% 4-(1,1,3,6-tetramethyl-Z-cyclohexen-Z-yl) 4 mercapto-butanone-2. The crude product is fractionally distilled, whereby there are obtained 9.75 g. of 4-(1,1,3, 6tetramethyl 2 cyclohexen- 2-yl) 4 mercapto-butanone-2 of boiling point 102 C./ 0.1 mm. Hg and of 96% purity.

EXAMPLE 7 1 g. of 'y-ionone are dissolved in 2 ml. of thioacetic acid and treated with 10 mg. of azodiisobutyronitrile. The mixture is heated at C. for 2 hours. The mixture is fractionally distilled at 0.01 mm. Hg. There are obtained 530 mg. of 4(1,l-dimethyl 3 methylene-cyclohex-Z-yl)-4- acetyl-mercapto-butanone-Z of boiling point C./ 0.01 mm. Hg (bulb-tube distillation).

EXAMPLE 8 1.6 g. of y-ionone are treated with a solution of 0.5 g. of potassium hydroxide in 5 ml. of absolute ethanol and cooled to -75 C. At this temperature, 40 ml. of hydrogen sulphide are condensed in over the course of 1 hour. The reaction solution is rapidly transferred into a precooled autoclave and heated to 50 C. (internal temperature), whereby the pressure increases to 23 atmospheres. It is subsequently cooled to 10 C., the excess hydrogen sulphide evaporated off and the residual reaction mixture takeniup in 1 litre of ether. The ethereal solution is washed four times with 50 ml. of saturated aqueous sodium chloride solution each time and then dried over anhydrous magnesium sulphate. After distillation of the ether under a vacuum, there remains a crude product (1.75 g.) which, according to gas-chromatographic analysis, consists of 48% 'y-ionone and 52% 4-(l,1-dimethyl- 3 methylenecyclohex-2-yl)-4-mercapto-butanone-2 (in the form of two diastereomers in the ratio 10:1). The crude product is fractionally distilled, whereby there are obtained 250 mg. of 4-(1,1-dimethyl-B-methylene-cyclohex-2-yl) 4 mercapto-butanone-2 of boiling point 95 C./ 0.02 mm. Hg (bulb-tube distillation).

The following examples illustrate odorant and/or fiavouring compositions containing the ionone and irone derivatives provided by the invention:

EXAMPLE A To a raspberry aroma composition consisting of Parts by weight ct-Irone 20 Vanillin 200 p-Hydroxyphenyl-butan-2-one (raspberry ketone) 500 Raspberry distillate 200 Isobutyric acid maltyl ester 40 Anthranilic acid methyl ester 0.5 Tiglic acid benzyl ester 0.5

there are added:

Parts by weight 4-(l,1,3-trimethyl 3 cyclohexen-Z-yl)-4-mercaptobutanone-2 1.84 4-(1,1,3-trimethyl 3 cyclohexen-Z-yl)-4-acetylrnercapto-butanone-Z 0.16 a-Ionone 200 This addition results in a marked improvement of the aroma in that the natural note of fresh raspberries is imparted to the composition.

EXAMPLE B To a raspberry aroma composition consisting of Parts by weight u-Irone 20 Vanillin 200 p-Hydroxyphenyl-butan-2-one 500 Maltol 200 Formic acid 150 Acetic acid 150 Acetic acid butyl ester 1 Acetic acid ethyl ester 0.5 Dimethyl sulphide 1 Benzyl alcohol 200 Menthone 1 C-14 aldehyde 10 C16 aldehyde 35 Raspberry distillate 200 Isobutyric acid maltyl ester 40 Anthranilic acid methyl ester 0.5 Tiglic acid benzyl ester 0.5

there is added one of the following mixtures:

Parts by weight a-Ionone 195 4-(1,1,3-trimethyl 3 cyclohexen-Z-yl)-4-acetylmercapto-butanone-Z 7 Parts by weight OL-IOl'lOl'lC 200 4-(1,1,3-trimethy1 3 cyclohexen-Z-yl)-4-mercaptobutanone-2 2 Parts by weight or-Ionone 190 4-(1,1,3-trimethyl 2 cyclohexen-Z-yl)-4-acetylmer capto-butanone-2 5 The addition of each of three mixtures results in a marked improvement of the aroma in the pronounced natural note of fresh raspberries is imparted to the composition.

EXAMPLE C To an odorant composition of the rose type consisting of 09 aldehyde 1% in phthalic acid diethyl ester) 1d Phenylacetaldehyde (10% in phthalic acid diethyl Phenylethyl alcohol extra 300 there are added 30 50 g. of a 10% solution of a-ionone, 4-(1,l,3-trimethyl-3-cyclohexen 2 yl) 4 mercaptobutanone-2 and 4-(1,1,3-trimethyl-3-cyclohexen-2-y1)4- acetylmercaptobutanone-Z in the proportion 75:23:2.

This addition has a rounding-off action and imparts a natural fullness to the composition.

EXAMPLE D A sugar syrup consisting of Percent Saccharose 30 Citric acid 1 Raspberry juice concentrate 20 Water 49 is treated with 0.1% of one of mixtures (1), (2) and (3) described in Example B. This aromatised sugar syrup is diluted with a five-fold amount of water and the resulting drink is carbonated with three volumes of carbon dioxide. The sparkling drink thus obtained has a fruityraspberry flavour which is immediately reminiscent of freshly crushed raspberries.

EXAMPLE E To a raspberry aroma composition consisting of Parts by weight ot-Irone 20 Vanillin 200 p-Hydroxyphenyl-butan-Z-one (raspberry ketone) 500 Maltol 200 Formic acid Acetic acid 150 Acetic acid butyl ester 1 Acetic acid ethyl ester 0.5 Dimethyl sulphide 1 Benzyl alcohol 200 Menthone 1 C-l4 aldehyde 10 C-l6 aldehyde 35 Raspberry distillate 200 Isobutyric acid maltyl ester 40 Anthranilic acid methyl ester 0.5 Tiglic acid benzyl ester 0.5

there is added one of the following mixtures:

Parts by weight 4(l,l,3-trimethyl 3 cyclohexen 2 yl) 4 mercaptobutanone 2 1.80 4-(1,1,3-trimethyl-3-cyclohexen 2 yl) 4 acetylmercapto butanone 2 0.18 ,8 Ionone 200 Parts by weight 4-(1,1,3,6-tetramethyl 3 cyclohexen 2 yl) 4- mercapto butanone 2 a Irone 200 Parts by weight 4-(1,l,3,6-tetran1ethyl-2 cyclohexen 2 yl) 4- mercapto butaneone 2 [3 Irone 201 This addition results in a marked improvement of the aroma in that the natural note of fresh raspberries is imparted to the composition.

9 EXAMPLE F To a raspberry aroma composition consisting of Parts by wei ht u-Irone 20 Vanillin 200 p-Hydroxyphenyl-butan-2-one (raspberry ketone) 500 Maltol 200 Formic acid 150 Acetic acid 150 Acetic acid butyl ester -5 1 Acetic acid ethyl ester 0.5 Dimethyl sulphide 1 Benzyl alcohol 200 Menthone 1 C14 aldehyde 10 C-16 aldehyde 35 Raspberry distillate 200 Isobutyric acid maltyl ester 40 Anthranilic acid methyl ester 0.5 Tiglic acid benzyl ester 0.5

there are added:

Parts by weight 4-(1,l-dimethyl 3 methylene-cyclohex 2 yl)-4- mercapto-butanone-Z 1.84 u-Ionone 200 10 This addition results in a marked improvement of the aroma in that the natural note of fresh raspberries is imparted to the composition.

What is claimed is: 1. A compound having the general formula SH 0 II 2,586,306 2/1952 Copenhaver 260609 D X BERNARD HELFIN, Primary Examiner N. P. MORGENSTERN, Assistant Examiner US. Cl. X.R.

UNITED STATES PATENT OFFICE CERTIFICATE OF CORRECTION Patent NO. 3,845,154 Dated October 29, 1974 inventor) Daniel Hel mlinger et a1 It is certified that error appears in the aboveidentified patent and that said Letters Patent: are hereby corrected as shown below:

Column 1 Formula (I) should appear as shown below:

UNITED STATES PATENT OFFICE CERTIFICATE OF CORRECTION lnventofls) Danlel Helmlrnger Page 2 It is certified that error appears in the above-identified patent and that said Letters Patent are hereby corrected as shown below:

Column 2, Formula (Ic) should appear as shown below:

Signed and Scaled this Arrest:

RUTH C. MASON C. MARSHALL DANN Atrzsring Officer (umml'ssium'r HflrJIUHIS and Trmlwnurkx 

1. A COMPOUND HAVING THE GENERAL FORMULA 